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Background Part of Masters Degree Pharmaceutical care rendered Aminophylline identified as a difficult drug Caffeine introduced as an alternative Study done to confirm safety and efficacy in this population

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Introduction What do we know? ↔Apnoeic attacks ↔ Gestational age inverse correlation : – Less than 30 weeks most infants – weeks an incidence of 50 % – weeks an incidence of 10 %

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Introduction (2) Apnoeic attacks also linked to birth weight : –Less than 1000g an incidence of 80% –Less than 2500g an incidence of 25%

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What treatment is available… Methylxanthines CaffeineAminophylline Mechanism of action…

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Mechanism of action (2) Acts via adenosine antagonism to increase the sensitivity of respiratory centers to carbon dioxide, and to increase the contractility of respiratory muscles Apnoea

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Common Adverse Effects Central nervous system side effects –Irritability –Jitteriness Cardio-vascular system side effects –Tachycardia Gastrointestinal side effects –Feeding intolerance Respiratory system side effects –Tachypnoea

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Aim and objectives Aim: To determine the comparative efficacy of aminophylline and caffeine in the prevention of apnoea in premature infants in the neonatal intensive care unit Objectives: –To determine the safety profile of aminophylline versus caffeine in the prevention of apnoea of prematurity (AOP) –To determine the efficacy of aminophylline versus caffeine in the prevention of AOP

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Respiratory System Profile (1) The median respiratory rate was significantly higher in the aminophylline group than in the caffeine group on five study days (Days 3, 4, 5, 7 and 8) (Wilcoxon two-sample test) Respiratory Rate Respiratory Rate

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Respiratory System Profile (3) Saturation Saturation monitored 3 hourlySaturation monitored 3 hourly No statistical difference between the 2 groups in terms of the number of patients saturation levels below 92% or below 80%No statistical difference between the 2 groups in terms of the number of patients saturation levels below 92% or below 80%

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Patient-days on the following were compared:Patient-days on the following were compared: –Breast feeding (BF) –Expressed breast milk feeding (EBM) –Formula Feeding (FM) –Nil per Os (NPO) –Total Parenteral Nutrition (TPN) Gastrointestinal System Nutritional Support Nutritional Support

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Gastrointestinal System Aspirates Aspirates Followed for 153 days Followed for 175 days Aspirates recorded for 112 days Aspirates recorded for 136 days Aspirates > 30% of intake: 9 days Aspirates > 30% of intake: 13 days Statistical difference for aspirates > 30% of intake: None (Chi square test) AminophyllineCaffeine 73% 6% 77% 7%

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Gastrointestinal System Diarrhoea:Diarrhoea: –3 patients on aminophylline –1 patient on caffeine Bloody Aspirates:Bloody Aspirates: –Equal in both groups Vomiting:Vomiting: –Two patients in each group, but for the aminophylline patients one day longer Other Other

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Central Nervous System Side effects often noted with clinical toxicity due to supra-therapeutic levels; no supra-therapeutic levels recorded for the study Parameters monitored: –Irritability –Jitteriness None were observed in either of the treatment arms

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Conclusions Caffeine caused fewer cardiovascular and respiratory side effects. Gastrointestinal side effects were comparable between oral caffeine and IV aminophylline. Oral caffeine is more convenient to administer and may facilitate breastfeeding. Oral caffeine is an effective alternative to aminophylline in preventing apnoeic attacks.

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Acknowledgements Babies and their parents for participating in the study Doctors and nurses in the NICU for their cooperation Monika Zweygarth for assistance with the analysis of the data Medical Research Council for financial support Department of Pharmacy for logistical support